What is sickle cell anemia?
Sickle cell anemia is a genetic disease of the blood, so defined by the characteristic sickle shape taken, in particular circumstances, by the sick red blood cells. This peculiarity is in contrast with the typical shape - a biconcave disk, elastic and easily deformable - of mature erythrocytes, which allows them to pass undisturbed in the narrow lumen of the blood capillaries.
Not surprisingly, the average life of half-moon erythrocytes is 10-20 days, compared to 4 months in normal red blood cells. The consequences of sickle cell anemia are therefore linked to the increase in blood viscosity, to the reduction of the amount of oxygen available to the tissues and to the appearance of vaso-occlusive phenomena.
As anticipated, the sickling of red blood cells occurs mainly in certain precipitating situations, including hypoxia, decreased blood pH, severe infections, increased temperature and the presence of 2, 3 bisphosphoglyceric acid. These conditions are typical of the venous portion of the capillaries and increase, for example, during strenuous exercise and in high mountain living.
Index Further information
Causes of Sickle Cell Anemia Symptoms and Complications Treatment and Treatment Medicines for the Treatment of Sickle Cell AnemiaCauses
Sickle cell anemia is caused by a mutation of the gene that directs the synthesis of hemoglobin, a large protein that captures oxygen from the lungs and transports it to various tissues. Inside the red blood cells, the hemoglobin also collects a part of the carbon dioxide and transports it to the lungs, where it is eliminated.
In the adult, each hemoglobin molecule has - in its quaternary structure - four subunits, of which two alpha chains, identical, of 141 amino acids, and two Beta chains, identical, of 146 amino acids.
In sickle-cell anemia the mutation involves a single nucleotide base of the gene that codes for the Beta subunit. This mutation (an adenine replaces a thymine) causes the replacement of one amino acid (glutamic acid) with another (valine).
The result is an abnormal form of hemoglobin - called hemoglobin S (from sickle, an English word meaning sickle) - with different physico-chemical structure and characteristics. In the presence of low oxygen tension, hemoglobin S polymerizes; consequently the erythrocytes lengthen and sag, taking on the characteristic sickle shape.
As anticipated, sickle cell anemia is an inherited disease and as such is not contagious, nor is it secondary to infectious diseases or food shortages. On the contrary, it has been present since birth. From a genetic point of view, it is an autosomal recessive disease; this means that patients with sickle cell disease are homozygous for the mutation. Heterozygous individuals, that is, who receive a mutated gene from one parent and its healthy allele on the other, are instead asymptomatic (if not exposed to serious oxygen deficiencies, they do not present haemolysis, anemia, painful crises or thrombotic complications). Even in the absence of anemia, in heterozygotes the sickle cell trait (falcemia) can be demonstrated in vitro; in these individuals only one percent of the circulating red blood cells have an abnormal shape, while in homozygotes this percentage rises up to 50%.
Risk of Sending Disease to Children
Sickle-cell anemia is particularly widespread in some areas of the globe, particularly in the Mediterranean regions (especially in Africa) and more generally in those where malaria is still present or was in the past. In fact, depranocytosis has a protective effect against this mosquito-borne disease. About 0.2-0.3% of black Americans are homozygous for the disease, while heterozygotes account for 8-13% of the black population.
To help these couples, special in vitro fertilization methods have been developed, through which the eggs taken from the mother are fertilized with the sperm of the father. The zygotes are then subjected to a test to detect the presence of the abnormal gene; in this way only the fertilized ova lacking the mutation are transferred to the mother's uterus, due to the implantation and the normal continuation of the pregnancy. However, this intervention has its limitations, represented by the high cost and the absence of certainties on the positive outcome.
Healthy carriers of the mutated gene for sickle cell anemia are easily identified by a simple blood test; it is also possible to carry out prenatal diagnosis. In couples where at least one of the partners belongs to a family at risk, an interview with a genetic counselor is essential to evaluate the possibilities of giving birth to children affected by the disease.
From the relationship between an individual heterozygous for the gene responsible for sickle cell disease and another perfectly healthy from this point of view, healthy children or with absolutely normal hemoglobin can be born; the probability, for both cases, is 50% with each pregnancy.